LEPTOSPIROSIS - An Overview

Practice Essentials

Leptospirosis is an infectious disease of humans and animals that is caused by pathogenic spirochetes of the genus Leptospira. It is considered the most common zoonosis in the world.

Signs and symptoms

Leptospirosis occurs as two recognizable clinical syndromes: anicteric and icteric. Anicteric leptospirosis is a self-limited, mild flulike illness characterized by sudden onset of some combination of the following:

• Headache
• Fever (38-40°C)
• Rigors
• Muscle pain (typically localized to the calf and lumbar areas)
• Nausea and vomiting
• Anorexia
• Diarrhea
• Cough
• Pharyngitis
• Conjunctivitis
• Nonpruritic rash

Icteric leptospirosis, also known as Weil disease, is a severe illness whose classic manifestations include the following:

• Fever
• Jaundice
• Renal failure
• Hemorrhage

Other organ systems (ie, pulmonary, cardiac system, central nervous system) are also frequently involved.

Diagnosis

Laboratory studies used to confirm the diagnosis include the following:

• Culture of leptospires from body fluids or tissue (criterion standard)
• Microscopic agglutination testing (MAT; the criterion standard for serologic identification of leptospires, available only at reference laboratories)

Studies to determine the extent of organ involvement and severity of complications may include the following, depending on the clinical presentation:

• CBC
• Renal function studies
• Coagulation studies
• Liver function studies
• CSF analysis
• Chest radiography
• Biliary tract ultrasonography
• ECG

Management

Use of antibiotics in mild leptospirosis is controversial. If used, antibiotic treatment may include the following:

• Doxycycline
• Ampicillin
• Amoxicillin

Antibiotics for severe leptospirosis include the following:

• IV penicillin G (long the drug of choice)
• Third-generation cephalosporins (cefotaxime and ceftriaxone)
• Ampicillin or amoxicillin (second-line agents)
• Erythromycin (in penicillin-allergic pregnant women)

Patients with severe cases also require supportive therapy and careful management of renal, hepatic, hematologic, and central nervous system complications. If renal failure ensues, corticosteroids may be considered. Additional supportive care may include inotropic agents, diuretics, or ophthalmic drops.

Approach Considerations

Antimicrobial therapy is indicated for the severe form of leptospirosis, but its use is controversial for the mild form of leptospirosis. A Cochrane Review found insufficient evidence to advocate for or against the use of antibiotics in the therapy for leptospirosis.

If antibiotics are used, they should be initiated as soon as the diagnosis of leptospirosis is considered and should be continued for a full course despite initial serologic results, because most patients are diagnosed only through acute and convalescent testing. Early treatment has been shown to offer the best clinical outcomes; results from controlled studies of treatment during the immune phase have yielded mixed results.

Mild leptospirosis is treated with doxycycline, ampicillin, or amoxicillin. For severe leptospirosis, intravenous penicillin G has long been the drug of choice, although the third-generation cephalosporins cefotaxime and ceftriaxone have become widely used. Alternative regimens are ampicillin, amoxicillin, or erythromycin. Several other antibiotics may be useful—for example, broth microdilution testing has shown sensitivity to macrolides, fluoroquinolones, and carbapenems —but clinical experience with these agents is more limited.

Severe cases of leptospirosis can affect any organ system and can lead to multiorgan failure. Supportive therapy and careful management of renal, hepatic, hematologic, and central nervous system complications are important.

Patients should be managed in a monitored setting because their condition can rapidly progress to cardiovascular collapse and shock. Access to mechanical ventilation and airway protection should be available in the event of respiratory compromise. Continuous cardiac monitoring should be attained; arrhythmias, including ventricular tachycardia and premature ventricular contractions, as well as atrial fibrillation, flutter, and tachycardia, can occur.

Renal function should be evaluated carefully and dialysis considered in cases of renal failure. In most cases, the renal damage is reversible if the patient survives the acute illness. A few cases in the literature have reported that plasma exchange, corticosteroids, and intravenous immunoglobulin may be beneficial in selected patients in whom conventional therapy does not elicit a response.

Corticosteroid therapy with high-dose pulsed methylprednisolone (30 mg/kg/d, not to exceed 1500 mg has been used successfully to treat patients with leptospiral renal failure without dialysis. This approach may have an important role in areas of the world with limited resources where dialysis treatment is unavailable and would involve lengthy medical transport. The use of renal-dose dopamine in conjunction with steroids or diuretics has also been described.

Pulse-dose steroids may also play a role in the management of severe pulmonary disease. Patients with Weil syndrome may need transfusions of whole blood, platelets, or both. Ophthalmic drops of mydriatics and corticosteroids have been used for relief of ocular symptoms.

Patients with severe disease should remain hospitalized until adequate resolution of organ failure and clinical infection. Outpatient follow-up may include an assessment of renal function to ensure ongoing reversal of any damage. A cardiac assessment may be indicated in patients with symptoms suggestive of heart involvement.

Diet and Activity

In mild cases, patients should be encouraged to maintain adequate fluid intake to avoid volume depletion. In more severe cases, diets appropriate for the clinical picture should be ordered (eg, electrolyte and protein restriction in cases of renal insufficiency). Patients with hypotension or clinical shock should not be fed enterally until adequate perfusion is restored.

Patients with severe disease should be placed on bed rest until adequately resuscitated and treated. Those with mild disease can pursue activity as tolerated.

Transfer

Transfer to a facility with an appropriate level of care should be considered in patients with severe disease. Leptospirosis has a regional epidemiology with high incidence of cases in remote regions that offer limited medical care. Although transporting patients with severe disease to appropriate medical centers is preferred, military physicians who have treated patients from Western Pacific islands averted the need for transoceanic transport for dialysis by administering high-dose steroids.

Consultations

In severe cases of leptospirosis, several specialty consultations may aid in proper patient management. An infectious disease specialist may assist in differentiating leptospirosis from diseases with similar presentations but that may have significantly different treatments. A nephrologist should be alerted early in the course because the need for dialysis may develop rapidly. If available, critical care specialists may be best prepared to manage patients with affected multiple systems.

For assistance with laboratory diagnosis, the Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) can aid the clinician in obtaining samples and ordering tests

Deterrence/Prevention

Prevention of leptospirosis is difficult because the organism has not been eradicated from wild animals, which constantly infect domestic animals. Important control measures include control of livestock infection with good sanitation, immunization, and proper veterinary care.

Preventing infected animals from urinating in waters where humans have contact, disinfecting contaminated work areas, providing worker education, practicing good personal hygiene, and using personal protective equipment (PPE) when handling infected animals or tissues are important actions for prevention of the disease. Examples of PPE include gloves and face shields for veterinarians and rubber boots for sewer workers and agricultural workers who wade in rodent urine-contaminated water.

Public health measures include investigation of cases in an effort to detect common source outbreaks and implementation of appropriate control measures to prevent further cases. Other public health measures include identification of contaminated water supplies, rodent control, prohibition of swimming in streams where risk of infection may be high, and informing people of risk when they are involved in recreational activities.

Vaccines are offered to high-risk workers in some European and Asian countries (eg, rice workers in Italy). Human vaccines are serovar specific and must be repeated yearly. They are associated with painful swelling, especially after revaccination. Vaccines are not used in the United States.

However, renal infection and persistent leptospiruria can occur in immunized dogs. Human infection has occurred from asymptomatic immunized dogs that still shed leptospires in their urine. Also, these animal vaccines are serovar specific and thus are useful only where one or a few serovars are present. Hence, the vaccine given should contain the serovars known to be prevalent in the area.

Doxycycline, in the dose of 200 mg every week, has demonstrated efficacy of 95% against leptospirosis and may help prevent the disease in exposed adults. This regimen is recommended for those with short-term exposure and is not for repeated or long-term exposure. The role of prophylaxis in children has not been adequately studied.

Medication Summary

Treatment for leptospirosis consists of empiric antibiotic therapy. In general, antibiotic therapy should be effective against leptospirosis and against the other pathogens considered in the differential diagnoses. If renal failure ensues, corticosteroids may be considered. Additional supportive care may include inotropic agents, diuretics, or ophthalmic drops. Currently, no human vaccine against leptospirosis is available.

Contributor Information and Disclosures

Author

Sandra G Gompf, MD, FACP, FIDSA  Associate Professor of Infectious Diseases and International Medicine, University of South Florida College of Medicine; Chief, Infectious Diseases Section, Director, Occupational Health and Infection Control Programs, James A Haley Veterans Hospital

Sandra G Gompf, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Ana Paula Velez, MD  Assistant Professor of Medicine, Division of Infectious Disease and International Medicine, University of South Florida College of Medicine and James A Haley Veterans Affairs Medical Center; Attending Physician, Moffitt Cancer Center

Ana Paula Velez, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Medical Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Judith Green-McKenzie, MD, MPH, FACP, FACOEM  Associate Professor, Director of Clinical Practice, Occupational Medicine Residency Director, University of Pennsylvania School of Medicine

Judith Green-McKenzie, MD, MPH, FACP, FACOEM is a member of the following medical societies:American College of Occupational and Environmental Medicine, American College of Physicians, American College of Preventive Medicine, and National Medical Association

Source: http://emedicine.medscape.com/